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Phenotype Ontology
Like Gene Ontology (GO), phenotypy ontology classifies and organizes gene-mutant/null phenotypic information from the very general at the top to more specific terms in the directed acyclic graph (DAG) by viewing an individual term as a node and its relations to parental terms (allowing for multiple parents) as directed edges. To navigate this hierarchy, we display all parental phenotypic terms to the current phenotypic term of interest ordered by their shortest distances to the current term. Also, only direct children phenotypic terms of the current phenotypic term are listed. Phenotype ontologies we have incorporated are as follows:

• Disease Ontology (DO) Ontology (DO)
  DO semantically integrates disease and medical vocabularies through extensive cross mapping of DO terms to MeSH, ICD, NCI thesaurus, SNOMED and OMIM.
  
• Human Phenotype (HP) Ontology (HP)
  HP captures phenotypic abnormalities that are described in OMIM, along with the corresponding disease-causing genes. It includes three complementary biological concepts: Mode_of_Inheritance (MI), ONset_and_clinical_course (ON), and Phenotypic_Abnormality (PA).
  
• Mouse Phenotype (MP) Ontology (MP)
  MP describes phenotypes of the mouse after a specific gene is genetically disrupted. Using it, Mouse Genome Informatics (MGI) provides high-coverate gene-level phenotypes for the mouse.
  
• Worm Phenotype (WP) Ontology (WP)
  WP classifies and organizes phenotype descriptions for C. elegans and other nematodes. Using it, WormBase provides primary resource for phenotype annotations for C. elegans.
  
• Yeast Phenotype (YP) Ontology (YP)
  Based on YP which is the major contributor to the Ascomycete phenotype ontology, Saccharomyces Genome Database (SGD) provides single mutant phenotypes for every gene in the yeast genome.
  
• Fly Phenotype (FP) Ontology (FP)
  FP refers to FlyBase controlled vocabulary. Specifically, a structured controlled vocabulary is used for the annotation of alleles (for their mutagen etc) in FlyBase.
  
• Fly Anatomy (FA) Ontology (FA)
  FA is a structured controlled vocabulary of the anatomy of Drosophila melanogaster, used for the description of phenotypes and where a gene is expressed.
  
• Zebrafish Anatomy (ZA) Ontology (ZA)
  ZA displays anatomical terms of the zebrafish using standard anatomical nomenclature, together with affected genes.
  
• Xenopus Anatomy (XA) Ontology (XA)
  XA represents the lineage of tissues and the timing of development for frogs (Xenopus laevis and Xenopus tropicalis). It is used to annotate Xenopus gene expression patterns and mutant and morphant phenotypes.
  
• Arabidopsis Plant Ontology (AP) Ontology (AP)
  As a major contributor to Plant Ontology which describes plant anatomical and morphological structures (AN) and growth and developmental stages (DE), the Arabidopsis Information Resource (TAIR) provides arabidopsis plant ontology annotations for the model higher plant Arabidopsis thaliana.
  
• Enzyme Commission (EC) Ontology (EC)
  Each enzyme is allocated a four-digit EC number, the first three digits of which define the reaction catalysed and the fourth of which is a unique identifier (serial number). Each enzyme is also assigned a systematic name that uniquely defines the reaction catalysed.
  
• DrugBank ATC (DB) Ontology (DB)
  In the Anatomical Therapeutic Chemical (ATC) classification system, drugs are classified in groups at five different levels according to the organ or system (1st level, anatomical main group) on which they act and their therapeutic (2nd level, therapeutic subgroup), pharmacological (3rd level, pharmacological subgroup) and chemical properties (4th level, chemical subgroup; 5th level, chemical substance). Only drugs in DrugBank are considered.
  
• UniProtKB KeyWords (KW) Ontology (KW)
  Keywords in UniProtKB are controlled vocabulary, providing a summary of the entry content and are used to index UniProtKB/Swiss-Prot entries based on 10 categories (the category "Technical term" being excluded here). Each keyword is attributed manually to UniProtKB/Swiss-Prot entries and automatically to UniProtKB/TrEMBL entries (according to specific annotation rules).
  
• UniProtKB UniPathway (UP) Ontology (UP)
  UP is a fully manually curated resource for the representation and annotation of metabolic pathways, being used as controlled vocabulary for pathway annotation in UniProtKB.
  

Structural Domain Phenotype Ontology and its Annotations
Structural Classification of Proteins (SCOP) classifies evolutionary-related domains into Superfamily level and Family level. Using the phenotype ontologies above, we have generated the domain-centric phenotype annotations, and further identified those phenotype terms which are the most informative to annotate SCOP domains. Promisingly, domain-centric phenotypic annotations can serve as an alternative starting point to explore genotype-phenotype relationships. We provide several relevant files for the download, including the annotation and the corresponding ontology for each phenotype ontology.

• Structural Domain Disease Ontology (DO) Ontology (SDDO) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2DO.txt, and the corresponding ontology:SDDO.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Human Phenotype (HP) Ontology (SDHP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2HP.txt, and the corresponding ontology:SDHP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Mouse Phenotype (MP) Ontology (SDMP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2MP.txt, and the corresponding ontology:SDMP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Worm Phenotype (WP) Ontology (SDWP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2WP.txt, and the corresponding ontology:SDWP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Yeast Phenotype (YP) Ontology (SDYP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2YP.txt, and the corresponding ontology:SDYP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Fly Phenotype (FP) Ontology (SDFP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2FP.txt, and the corresponding ontology:SDFP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Fly Anatomy (FA) Ontology (SDFA) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2FA.txt, and the corresponding ontology:SDFA.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Zebrafish Anatomy (ZA) Ontology (SDZA) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2ZA.txt, and the corresponding ontology:SDZA.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Xenopus Anatomy (XA) Ontology (SDXA) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2XA.txt, and the corresponding ontology:SDXA.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Arabidopsis Plant Ontology (AP) Ontology (SDAP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2AP.txt, and the corresponding ontology:SDAP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Enzyme Commission (EC) Ontology (SDEC) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2EC.txt, and the corresponding ontology:SDEC.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain DrugBank ATC (DB) Ontology (SDDB) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2DB.txt, and the corresponding ontology:SDDB.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain UniProtKB KeyWords (KW) Ontology (SDKW) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2KW.txt, and the corresponding ontology:SDKW.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain UniProtKB UniPathway (UP) Ontology (SDUP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2UP.txt, and the corresponding ontology:SDUP.txt) and mysql tables (Domain2PO.sql.gz).
  

Supra-domain Phenotype Ontology and its Annotations
Although domain-centric annotations hold great promise in describing phenotypic nature of independent domains, most domains themselves may not just work alone. In multi-domain proteins, they may be combined together to form distinct domain architectures. The recombination of the existing domains is considered as one of major driving forces for phenotypic diversificaation. As an extension, we have also generated supra-domain phenotype ontology and its annotations. Compared to domain-centric phenotype ontology and annotations (SCOP domains at the Superfamily level and Family level), this version focuses on supra-domains and individual SCOP domains ONLY at the Superfamily level. Besides, in terms of individual superfamilies, their annotations from the domain-centric version may be different from those from supra-domains version. Depending on your focus, the former should be used for the consideration of both the Superfamily level and Family level, otherwise the latter should be used if you are interested in domain combinations. Also, we provide several relevant files for the download, including the annotation and the corresponding ontology for each phenotype ontology.

• Supra-domain Domain Disease Ontology (DO) Ontology (SPDO) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2DO.txt, and the corresponding ontology:SPDO.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Human Phenotype (HP) Ontology (SPHO) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2HP.txt, and the corresponding ontology:SPHO.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Mouse Phenotype (MP) Ontology (SPMP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2MP.txt, and the corresponding ontology:SPMP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Worm Phenotype (WP) Ontology (SPWP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2WP.txt, and the corresponding ontology:SPWP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Yeast Phenotype (YP) Ontology (SPYP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2YP.txt, and the corresponding ontology:SPYP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Fly Phenotype (FP) Ontology (SPFP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2FP.txt, and the corresponding ontology:SPFP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Fly Anatomy (FA) Ontology (SPFA) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2FA.txt, and the corresponding ontology:SPFA.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Zebrafish Anatomy (ZA) Ontology (SPZA) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2ZA.txt, and the corresponding ontology:SPZA.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Xenopus Anatomy (XA) Ontology (SPXA) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2XA.txt, and the corresponding ontology:SPXA.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Arabidopsis Plant Ontology (AP) Ontology (SPAP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2AP.txt, and the corresponding ontology:SPAP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Enzyme Commission (EC) Ontology (SPEC) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2EC.txt, and the corresponding ontology:SPEC.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain DrugBank ATC (DB) Ontology (SPDB) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2DB.txt, and the corresponding ontology:SPDB.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain UniProtKB KeyWords (KW) Ontology (SPKW) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2KW.txt, and the corresponding ontology:SPKW.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain UniProtKB UniPathway (UP) Ontology (SPUP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2UP.txt, and the corresponding ontology:SPUP.txt) and mysql tables (SP2PO.sql.gz).
  

Superfamily domains annotated to this FA term (SDFA level: Least Informative)
Highlighted in gray are those with FDR_all>0.001

SCOP term	FDR (all)	Annotation (direct or inherited)
Integrin domains	0	DIRECT
L27 domain	0	DIRECT
Frizzled cysteine-rich domain	0	DIRECT
alpha-catenin/vinculin-like	0	DIRECT
Sema domain	0	DIRECT
lambda repressor-like DNA-binding domains	0	DIRECT
MIR domain	0	DIRECT
Acetyl-CoA synthetase-like	0	DIRECT
Cdc48 domain 2-like	0	DIRECT
Multidrug resistance efflux transporter EmrE	0	DIRECT
Rhodanese/Cell cycle control phosphatase	0	DIRECT
Clathrin adaptor appendage domain	0	DIRECT
SAP domain	0	DIRECT
SMAD MH1 domain	0	DIRECT
Second domain of Mu2 adaptin subunit (ap50) of ap2 adaptor	0	DIRECT
Metal cation-transporting ATPase, ATP-binding domain N	0	DIRECT
PreATP-grasp domain	0	DIRECT
Plexin repeat	0	DIRECT
A DNA-binding domain in eukaryotic transcription factors	0	DIRECT
PX domain	0	DIRECT
Histone H3 K4-specific methyltransferase SET7/9 N-terminal domain	0	DIRECT
Cysteine-rich DNA binding domain, (DM domain)	0	DIRECT
Cytokine	0	DIRECT
Integrin alpha N-terminal domain	0	DIRECT
Regulator of G-protein signaling, RGS	0	DIRECT
Kazal-type serine protease inhibitors	0	DIRECT
Conserved domain common to transcription factors TFIIS, elongin A, CRSP70	0	DIRECT
Periplasmic binding protein-like I	0	DIRECT
Putative DNA-binding domain	0	DIRECT
Smc hinge domain	0	DIRECT
Rhomboid-like	0	DIRECT
SAICAR synthase-like	0	DIRECT
Serpins	0	DIRECT
cAMP-binding domain-like	0	DIRECT
TIMP-like	0	DIRECT
Second domain of FERM	0	DIRECT
RCC1/BLIP-II	0	DIRECT
ADC-like	0	DIRECT
Mob1/phocein	0	DIRECT
ARID-like	0	DIRECT
Homeodomain-like	0.00000000003154	DIRECT
beta-beta-alpha zinc fingers	0.000006204	DIRECT
HLH, helix-loop-helix DNA-binding domain	0.00005896	DIRECT
Immunoglobulin	0.0004112	DIRECT
Fibronectin type III	0.0008443	DIRECT
Glucocorticoid receptor-like (DNA-binding domain)	0.005808	INHERITED FROM: region of integument || adult external thorax
Protein kinase-like (PK-like)	0.007492	INHERITED FROM: intestinal stem cell || photoreceptor cell R8 of pale ommatidium || synaptic neuropil || adult midgut epithelium
Nuclear receptor ligand-binding domain	0.01034	INHERITED FROM: mushroom body || mushroom body gamma-lobe || adult MBp lineage clone || neuropil || adult MBp lineage neuron || supraesophageal ganglion neuron || protocerebrum || synaptic neuropil || synaptic neuropil block
p53-like transcription factors	0.01034	INHERITED FROM: adult external thorax || mesothoracic tergum
SH2 domain	0.01071	INHERITED FROM: midline crossing tract || ommatidium || adult peripheral nervous system || wing blade || photoreceptor cell R7
HMG-box	0.04259	INHERITED FROM: adult external thorax || wing
Orange domain-like	0.06468	INHERITED FROM: EG neuron || 5-6I of thorax || EL neuron
EGF/Laminin	0.07472	INHERITED FROM: ocellus || ventral nervous system || tendon cell || embryonic precursor cell of adult midgut || eye photoreceptor cell stalk || proventriculus || wing blade || embryonic/larval midgut cell
Cystine-knot cytokines	0.08872	INHERITED FROM: embryonic/larval posterior spiracle || embryonic/larval spiracle || stigmatophore
Ankyrin repeat	0.1113	INHERITED FROM: Johnston organ neuron
vWA-like	0.1498	INHERITED FROM: endocuticular specialization || muscle attachment site
Transducin (alpha subunit), insertion domain	0.1971	INHERITED FROM: eo neuron
Toll/Interleukin receptor TIR domain	0.1971	INHERITED FROM: ventral nerve cord
Snake toxin-like	0.1971	INHERITED FROM: wing vein || wing cell || embryonic/larval neuromuscular junction
SET domain	0.2749	INHERITED FROM: metathoracic leg || haltere
Growth factor receptor domain	0.3029	INHERITED FROM: surface associated glial cell || ocellus || RP2sib neuron || dMP2 neuron || integumentary specialisation || ventral nervous system || embryonic fiber tract || wing vein L2 || ocellar triangle || vMP2 neuron || wing vein L4 || ventral midline || embryonic/larval midline of ventral nerve cord || retinal pigment cell || hindgut || proventriculus || articulation || photoreceptor cell R7
dsRNA-binding domain-like	0.3212	INHERITED FROM: alpha/beta Kenyon cell || antennal lobe projection neuron adPN || mushroom body extrinsic neuron || antennal lobe projection neuron iPN || Kenyon cell || unilateral ACT relay interneuron || persistent antennal lobe projection neuron || uniglomerular antennal lobe projection neuron
(Phosphotyrosine protein) phosphatases II	0.3487	INHERITED FROM: medial lobe of adult mushroom body || intersegmental nerve || lobe system of adult mushroom body
Cytochrome P450	0.3814	INHERITED FROM: embryonic/larval hindgut || commissure || tract neuropil || neuropil associated CNS glial cell || midgut || midline crossing tract || midline glial cell || embryonic/larval foregut || CNS glial cell || neuropil glial sheath || tract || hindgut
HAD-like	0.4753	INHERITED FROM: rhabdomere of eye photoreceptor cell
BAR/IMD domain-like	0.4753	INHERITED FROM: neuromuscular junction || NMJ bouton
Cadherin-like	0.532	INHERITED FROM: photoreceptor cell R4
Spectrin repeat	0.532	INHERITED FROM: longitudinal connective || ipsilateral tract || middle midgut || connective || midgut enterocyte || tract || copper cell

Family domains annotated to this FA term (SDFA level: Least Informative)
Highlighted in gray are those with FDR_all>0.001

SCOP term	FDR (all)	Annotation (direct or inherited)
Choline/Carnitine O-acyltransferase	0	DIRECT
Smc hinge domain	0	DIRECT
SAP domain	0	DIRECT
L27 domain	0	DIRECT
Serpins	0	DIRECT
Phoshoinositide 3-kinase (PI3K) helical domain	0	DIRECT
Acetyl-CoA synthetase-like	0	DIRECT
Histone H3 K4-specific methyltransferase SET7/9 N-terminal domain	0	DIRECT
ARID domain	0	DIRECT
L-arabinose binding protein-like	0	DIRECT
Second domain of FERM	0	DIRECT
Extracellular domain of cell surface receptors	0	DIRECT
Sema domain	0	DIRECT
Arrestin/Vps26-like	0	DIRECT
Rel/Dorsal transcription factors, DNA-binding domain	0	DIRECT
POU-specific domain	0	DIRECT
Cysteine-rich DNA binding domain, (DM domain)	0	DIRECT
Phosphate binding protein-like	0	DIRECT
First domain of FERM	0	DIRECT
Plexin repeat	0	DIRECT
Forkhead DNA-binding domain	0	DIRECT
RNase III catalytic domain-like	0	DIRECT
Ubiquitin carboxyl-terminal hydrolase, UCH	0	DIRECT
Phosphatidylinositol phosphate kinase IIbeta, PIPK IIbeta	0	DIRECT
Conserved domain common to transcription factors TFIIS, elongin A, CRSP70	0	DIRECT
Myb/SANT domain	0	DIRECT
Second domain of Mu2 adaptin subunit (ap50) of ap2 adaptor	0	DIRECT
Frizzled cysteine-rich domain	0	DIRECT
Reprolysin-like	0	DIRECT
SPRY domain	0	DIRECT
Fibroblast growth factors (FGF)	0	DIRECT
Class II glutamine amidotransferases	0	DIRECT
Cdc48 domain 2-like	0	DIRECT
Laminin-type module	0	DIRECT
p120GAP domain-like	0	DIRECT
Ubiquitin carboxyl-terminal hydrolase UCH-L	0	DIRECT
Dachshund-homology domain	0	DIRECT
Transforming growth factor (TGF)-beta	0	DIRECT
Cell cycle control phosphatase, catalytic domain	0	DIRECT
Phoshoinositide 3-kinase (PI3K), catalytic domain	0	DIRECT
Metal cation-transporting ATPase, ATP-binding domain N	0	DIRECT
NF-kappa-B/REL/DORSAL transcription factors, C-terminal domain	0	DIRECT
cAMP-binding domain	0	DIRECT
Erythroid transcription factor GATA-1	0	DIRECT
Diacylglycerol kinase-like	0	DIRECT
Mob1/phocein	0	DIRECT
Rhomboid-like	0	DIRECT
A DNA-binding domain in eukaryotic transcription factors	0	DIRECT
MIR domain	0	DIRECT
Third domain of FERM	0	DIRECT
Pepsin-like	0	DIRECT
Integrin alpha N-terminal domain	0	DIRECT
Synaptotagmin-like (S variant)	0	DIRECT
SMAD MH1 domain	0	DIRECT
Eps15 homology domain (EH domain)	0	DIRECT
Regulator of G-protein signaling, RGS	0	DIRECT
Integrin domains	0	DIRECT
PX domain	0	DIRECT
Single strand DNA-binding domain, SSB	0	DIRECT
Homeodomain	0.0000000000002039	DIRECT
HLH, helix-loop-helix DNA-binding domain	0.0001009	DIRECT
Fibronectin type III	0.001206	INHERITED FROM: LNv neuron || commissure || tract neuropil || prothoracic leg sensillum || nerve || gustatory receptor neuron || leg taste bristle || prothoracic leg taste bristle chemosensory neuron || adult brain || dendritic arborizing neuron || synaptic neuropil || LN period neuron || s-LNv neuron || prothoracic leg taste bristle
Classic zinc finger, C2H2	0.00503	INHERITED FROM: region of integument
Protein kinases, catalytic subunit	0.005243	INHERITED FROM: intestinal stem cell || photoreceptor cell R8 of pale ommatidium
Nuclear receptor ligand-binding domain	0.0108	INHERITED FROM: mushroom body || mushroom body gamma-lobe || adult MBp lineage clone || neuropil || adult MBp lineage neuron || supraesophageal ganglion neuron || protocerebrum || synaptic neuropil || synaptic neuropil block
SH2 domain	0.01205	INHERITED FROM: midline crossing tract || ommatidium || adult peripheral nervous system || wing blade || photoreceptor cell R7
Nuclear receptor	0.0264	INHERITED FROM: mushroom body || mushroom body gamma-lobe || adult MBp lineage clone || adult MBp lineage neuron || supraesophageal ganglion neuron || synaptic neuropil block
HMG-box	0.04354	INHERITED FROM: adult external thorax || wing
Ngr ectodomain-like	0.0623	INHERITED FROM: intersegmental nerve branch ISNb of A1-7 || intersegmental nerve of A1-7 || abdominal intersegmental nerve
Paired domain	0.0623	INHERITED FROM: EG neuron || EL neuron || RP2 motor neuron
Higher-molecular-weight phosphotyrosine protein phosphatases	0.0623	INHERITED FROM: intersegmental nerve
Hairy Orange domain	0.08227	INHERITED FROM: EG neuron || EL neuron
I set domains	0.08497	INHERITED FROM: LNv neuron || supraesophageal ganglion || tract neuropil || prothoracic leg sensillum || gustatory receptor neuron || leg taste bristle || prothoracic leg taste bristle chemosensory neuron || segmental subdivision of organ system || adult brain || connective || dendritic arborizing neuron || antennal lobe glomerulus || synaptic neuropil || neuropil glial sheath || adult cerebral ganglion || synaptic neuropil block || s-LNv neuron || prothoracic leg taste bristle || interface glial cell
Histone lysine methyltransferases	0.109	INHERITED FROM: metathoracic leg || haltere
Ankyrin repeat	0.1303	INHERITED FROM: ventral multidendritic neuron || Johnston organ neuron
PLC-like (P variant)	0.1429	INHERITED FROM: dorsal multidendritic neuron ddaC || dorsal multidendritic neuron || mesothoracic tergum
BTB/POZ domain	0.1611	INHERITED FROM: prothoracic leg
Transducin (alpha subunit), insertion domain	0.1888	INHERITED FROM: eo neuron
Toll/Interleukin receptor TIR domain	0.1888	INHERITED FROM: ventral nerve cord
SMAD domain	0.2497	INHERITED FROM: wing vein || gut section || wing blade
SAM (sterile alpha motif) domain	0.2731	INHERITED FROM: metatarsus || mesothoracic leg || prothoracic metatarsus || sex comb || metatarsus of male prothoracic leg || prothoracic tarsal segment
Ubiquitin activating enzymes (UBA)	0.3289	INHERITED FROM: protocerebrum
Cytochrome P450	0.3883	INHERITED FROM: embryonic/larval hindgut || commissure || tract neuropil || neuropil associated CNS glial cell || midgut || midline crossing tract || midline glial cell || embryonic/larval foregut || CNS glial cell || neuropil glial sheath || tract || hindgut
Cyclin	0.4177	INHERITED FROM: tagmatic subdivision of organ system
Calponin-homology domain, CH-domain	0.4249	INHERITED FROM: abdominal segmental nerve
EGF-type module	0.4526	INHERITED FROM: ventral nervous system || adult external head || embryonic precursor cell of adult midgut || hindgut || proventriculus || articulation || wing blade || embryonic/larval midgut cell
Growth factor receptor domain	0.4585	INHERITED FROM: ocellus || integumentary specialisation || ocellar triangle || dorsocentral bristle || salivary gland || hindgut || proventriculus
Spectrin repeat	0.5374	INHERITED FROM: longitudinal connective || ipsilateral tract || middle midgut || connective || midgut enterocyte || tract || copper cell
BAR domain	0.6088	INHERITED FROM: NMJ bouton
Cadherin	0.6238	INHERITED FROM: outer photoreceptor cell || photoreceptor cell R4
G proteins	0.6299	INHERITED FROM: wing hair

Trees by TreeVector

A presence/absence matrix is generated using protein domain architecture data for all genomes in SUPERFAMILY. The PAUP software is used to produce a single, large tree topology using heuristic parsimony methods. Genome combinations, or specific clades, can be displayed as if individual trees had been produced. However, this data is extracted from the single large tree. This produces a higher quality topology than if the trees had been produced on their own, and allows the trees to be displayed instantly.

Supra-domains annotated to this FA term (SPFA level: Least Informative)
Highlighted in gray are those with FDR>0.001

Supra-domain (Single)	FDR (all)	Annotation (direct or inherited)
cAMP-binding domain-like	0	DIRECT
MIR domain	0	DIRECT
Smc hinge domain	0	DIRECT
Regulator of G-protein signaling, RGS	0	DIRECT
Metal cation-transporting ATPase, ATP-binding domain N	0	DIRECT
SMAD MH1 domain	0	DIRECT
Plexin repeat	0	DIRECT
Histone H3 K4-specific methyltransferase SET7/9 N-terminal domain	0	DIRECT
Cdc48 domain 2-like	0	DIRECT
ADC-like	0	DIRECT
Kazal-type serine protease inhibitors	0	DIRECT
Multidrug resistance efflux transporter EmrE	0	DIRECT
Second domain of FERM	0	DIRECT
Clathrin adaptor appendage domain	0	DIRECT
ARID-like	0	DIRECT
A DNA-binding domain in eukaryotic transcription factors	0	DIRECT
Frizzled cysteine-rich domain	0	DIRECT
Second domain of Mu2 adaptin subunit (ap50) of ap2 adaptor	0	DIRECT
Rhomboid-like	0	DIRECT
Putative DNA-binding domain	0	DIRECT
SAICAR synthase-like	0	DIRECT
Serpins	0	DIRECT
Periplasmic binding protein-like I	0	DIRECT
Cysteine-rich DNA binding domain, (DM domain)	0	DIRECT
RCC1/BLIP-II	0	DIRECT
Acetyl-CoA synthetase-like	0	DIRECT
PreATP-grasp domain	0	DIRECT
Integrin alpha N-terminal domain	0	DIRECT
lambda repressor-like DNA-binding domains	0	DIRECT
TIMP-like	0	DIRECT
alpha-catenin/vinculin-like	0	DIRECT
PX domain	0	DIRECT
Integrin domains	0	DIRECT
Sema domain	0	DIRECT
Cytokine	0	DIRECT
Conserved domain common to transcription factors TFIIS, elongin A, CRSP70	0	DIRECT
Mob1/phocein	0	DIRECT
L27 domain	0	DIRECT
Rhodanese/Cell cycle control phosphatase	0	DIRECT
SAP domain	0	DIRECT
Homeodomain-like	0.00000000002203	DIRECT
beta-beta-alpha zinc fingers	0.000004373	DIRECT
HLH, helix-loop-helix DNA-binding domain	0.00004191	DIRECT
Immunoglobulin	0.0002914	DIRECT
Fibronectin type III	0.000596	DIRECT
Glucocorticoid receptor-like (DNA-binding domain)	0.004195	INHERITED FROM: region of integument || adult external thorax
Protein kinase-like (PK-like)	0.005465	INHERITED FROM: synaptic neuropil || photoreceptor cell R8 of pale ommatidium || intestinal stem cell || adult midgut epithelium
p53-like transcription factors	0.007605	INHERITED FROM: mesothoracic tergum || integumentary process || tract || adult external thorax
Nuclear receptor ligand-binding domain	0.007605	INHERITED FROM: adult MBp lineage clone || adult MBp lineage neuron || mushroom body gamma-lobe || synaptic neuropil || mushroom body || supraesophageal ganglion neuron || neuropil || synaptic neuropil block || protocerebrum
SH2 domain	0.007884	INHERITED FROM: adult peripheral nervous system || photoreceptor cell R7 || ommatidium || connective || wing blade || midline crossing tract
HMG-box	0.03306	INHERITED FROM: adult external thorax || wing
Orange domain-like	0.05156	INHERITED FROM: EL neuron || EG neuron || 5-6I of thorax || nervous system of embryonic/larval thorax
EGF/Laminin	0.06016	INHERITED FROM: larval caeca region || embryonic/larval midgut cell || tendon cell || eye photoreceptor cell stalk || embryonic precursor cell of adult midgut || proventriculus || ventral nervous system || ocellus || wing blade
Cystine-knot cytokines	0.0723	INHERITED FROM: stigmatophore || spiracle || embryonic/larval posterior spiracle || embryonic/larval spiracle
Ankyrin repeat	0.09222	INHERITED FROM: Johnston organ neuron
vWA-like	0.1263	INHERITED FROM: muscle attachment site || endocuticular specialization
GTPase activation domain, GAP	0.1274	INHERITED FROM: abdominal intersegmental nerve
Toll/Interleukin receptor TIR domain	0.1698	INHERITED FROM: ventral nerve cord
Transducin (alpha subunit), insertion domain	0.1698	INHERITED FROM: eo neuron
Snake toxin-like	0.1698	INHERITED FROM: embryonic/larval neuromuscular junction || wing vein || adult optic lobe || wing cell
SET domain	0.2431	INHERITED FROM: haltere || metathoracic leg
Growth factor receptor domain	0.2701	INHERITED FROM: fascicle || ocellar triangle || RP2sib neuron || embryonic fiber tract || photoreceptor cell R7 || embryonic/larval midline of ventral nerve cord || surface associated glial cell || wing vein L2 || vMP2 neuron || proventriculus || dMP2 neuron || ventral midline || hindgut || integumentary specialisation || ventral nervous system || ocellus || articulation || wing vein L4 || retinal pigment cell
dsRNA-binding domain-like	0.2874	INHERITED FROM: alpha/beta Kenyon cell || unilateral ACT relay interneuron || uniglomerular antennal lobe projection neuron || Kenyon cell || persistent antennal lobe projection neuron || antennal lobe projection neuron iPN || antennal lobe projection neuron adPN || mushroom body extrinsic neuron
(Phosphotyrosine protein) phosphatases II	0.3149	INHERITED FROM: lobe system of adult mushroom body || intersegmental nerve || medial lobe of adult mushroom body
Cytochrome P450	0.3477	INHERITED FROM: midline glial cell || commissure || neuropil associated CNS glial cell || tract || tract neuropil || CNS glial cell || midgut || hindgut || embryonic/larval foregut || neuropil glial sheath || midline crossing tract || embryonic/larval hindgut
Calponin-homology domain, CH-domain	0.3774	INHERITED FROM: abdominal segmental nerve
BAR/IMD domain-like	0.4418	INHERITED FROM: NMJ bouton || neuromuscular junction
HAD-like	0.4418	INHERITED FROM: rhabdomere of eye photoreceptor cell || rhabdomere
Spectrin repeat	0.499	INHERITED FROM: ipsilateral tract || longitudinal connective || midgut enterocyte || tract || middle midgut || connective || copper cell
Cadherin-like	0.499	INHERITED FROM: photoreceptor cell R4

Supra-domains annotated to this FA term (SPFA level: Least Informative)
Highlighted in gray are those with FDR>0.001

Supra-domain (Duplex) in N- to C-terminal order	FDR (all)	Annotation (direct or inherited)
51045,51045 51045 - WW domain 51045 - WW domain	0	DIRECT
57903,57903 57903 - FYVE/PHD zinc finger 57903 - FYVE/PHD zinc finger	0	DIRECT
52440,56059 52440 - PreATP-grasp domain 56059 - Glutathione synthetase ATP-binding domain-like	0	DIRECT
69179,69179 69179 - Integrin domains 69179 - Integrin domains	0	DIRECT
47769,47769 47769 - SAM/Pointed domain 47769 - SAM/Pointed domain	0	DIRECT
101912,103575 101912 - Sema domain 103575 - Plexin repeat	0	DIRECT
48403,48403 48403 - Ankyrin repeat 48403 - Ankyrin repeat	0	DIRECT
52058,48726 52058 - L domain-like 48726 - Immunoglobulin	0	DIRECT
55550,56112 55550 - SH2 domain 56112 - Protein kinase-like (PK-like)	0	DIRECT
81660,56784 81660 - Metal cation-transporting ATPase, ATP-binding domain N 56784 - HAD-like	0	DIRECT
51206,51206 51206 - cAMP-binding domain-like 51206 - cAMP-binding domain-like	0	DIRECT
47220,47220 47220 - alpha-catenin/vinculin-like 47220 - alpha-catenin/vinculin-like	0	DIRECT
48371,56112 48371 - ARM repeat 56112 - Protein kinase-like (PK-like)	0	DIRECT
47031,50729 47031 - Second domain of FERM 50729 - PH domain-like	0	DIRECT
50044,55550 50044 - SH3-domain 55550 - SH2 domain	0	DIRECT
52777,52777 52777 - CoA-dependent acyltransferases 52777 - CoA-dependent acyltransferases	0	DIRECT
48425,50729 48425 - Sec7 domain 50729 - PH domain-like	0	DIRECT
57716,48508 57716 - Glucocorticoid receptor-like (DNA-binding domain) 48508 - Nuclear receptor ligand-binding domain	0	DIRECT
54236,47031 54236 - Ubiquitin-like 47031 - Second domain of FERM	0	DIRECT
47413,46689 47413 - lambda repressor-like DNA-binding domains 46689 - Homeodomain-like	0	DIRECT
49417,81296 49417 - p53-like transcription factors 81296 - E set domains	0	DIRECT
57903,47370 57903 - FYVE/PHD zinc finger 47370 - Bromodomain	0	DIRECT
50692,54585 50692 - ADC-like 54585 - Cdc48 domain 2-like	0	DIRECT
55550,50044 55550 - SH2 domain 50044 - SH3-domain	0	DIRECT
69318,69179 69318 - Integrin alpha N-terminal domain 69179 - Integrin domains	0	DIRECT
49562,49562 49562 - C2 domain (Calcium/lipid-binding domain, CaLB) 49562 - C2 domain (Calcium/lipid-binding domain, CaLB)	0	DIRECT
52058,52058 52058 - L domain-like 52058 - L domain-like	0	DIRECT
49265,49265 49265 - Fibronectin type III 49265 - Fibronectin type III	0	DIRECT
49562,48371 49562 - C2 domain (Calcium/lipid-binding domain, CaLB) 48371 - ARM repeat	0	DIRECT
57667,57667 57667 - beta-beta-alpha zinc fingers 57667 - beta-beta-alpha zinc fingers	0.00001284	DIRECT
48726,48726 48726 - Immunoglobulin 48726 - Immunoglobulin	0.006142	INHERITED FROM: prothoracic leg taste bristle || antennal lobe glomerulus || adult cerebral ganglion || synaptic neuropil || prothoracic leg taste bristle chemosensory neuron || tract neuropil || connective || s-LNv neuron || central nervous system || LNv neuron || synaptic neuropil block || leg taste bristle || adult brain
48726,49265 48726 - Immunoglobulin 49265 - Fibronectin type III	0.02505	INHERITED FROM: gustatory receptor neuron || lobe system of adult mushroom body || prothoracic leg taste bristle || antennal lobe glomerulus || adult antennal lobe glomerulus || neuropil associated CNS glial cell || prothoracic leg taste bristle chemosensory neuron || tract neuropil || giant fiber neuron || connective || s-LNv neuron || prothoracic leg sensillum || LNv neuron || leg taste bristle || neuropil glial sheath
47459,158457 47459 - HLH, helix-loop-helix DNA-binding domain 158457 - Orange domain-like	0.05156	INHERITED FROM: EL neuron || EG neuron || 5-6I of thorax || nervous system of embryonic/larval thorax
49899,49899 49899 - Concanavalin A-like lectins/glucanases 49899 - Concanavalin A-like lectins/glucanases	0.06976	INHERITED FROM: photoreceptor cell R4 || peripheral nervous system
47459,55785 47459 - HLH, helix-loop-helix DNA-binding domain 55785 - PYP-like sensor domain (PAS domain)	0.1698	INHERITED FROM: sclerite
57196,57184 57196 - EGF/Laminin 57184 - Growth factor receptor domain	0.1698	INHERITED FROM: wing vein || leg || photoreceptor cell R7 || intersegmental nerve || proventriculus || joint || integumentary specialisation || scutum || articulation || wing blade dorsal compartment || inner photoreceptor cell
47895,52540 47895 - Transducin (alpha subunit), insertion domain 52540 - P-loop containing nucleoside triphosphate hydrolases	0.1698	INHERITED FROM: eo neuron
81296,81296 81296 - E set domains 81296 - E set domains	0.2295	INHERITED FROM: abdominal segmental nerve || intersegmental nerve || segmental nerve || abdominal nerve || abdominal intersegmental nerve
46966,46966 46966 - Spectrin repeat 46966 - Spectrin repeat	0.3042	INHERITED FROM: ipsilateral tract || longitudinal connective || midgut enterocyte || tract || tract neuropil || middle midgut || connective || copper cell
50156,50044 50156 - PDZ domain-like 50044 - SH3-domain	0.3072	INHERITED FROM: embryonic/larval peripheral nervous system
52799,52799 52799 - (Phosphotyrosine protein) phosphatases II 52799 - (Phosphotyrosine protein) phosphatases II	0.3072	INHERITED FROM: nerve || abdominal segmental nerve || embryonic/larval peripheral nervous system || intersegmental nerve || segmental nerve || abdominal nerve
57184,57196 57184 - Growth factor receptor domain 57196 - EGF/Laminin	0.3803	INHERITED FROM: integumentary specialisation
57196,57196 57196 - EGF/Laminin 57196 - EGF/Laminin	0.3983	INHERITED FROM: ocellar triangle || intersegmental nerve branch ISNb of A1-7 || tertiary pigment cell || secondary pigment cell || eye photoreceptor cell stalk || postfrons || proventriculus || joint || ventral nervous system || ocellus || frons || articulation || wing blade dorsal compartment
49313,49313 49313 - Cadherin-like 49313 - Cadherin-like	0.5873	INHERITED FROM: photoreceptor cell R4 || outer photoreceptor cell || wing hair

Supra-domains annotated to this FA term (SPFA level: Least Informative)
Highlighted in gray are those with FDR>0.001

Supra-domain (Triple) in N- to C-terminal order	FDR (all)	Annotation (direct or inherited)
49899,49899,49899 49899 - Concanavalin A-like lectins/glucanases 49899 - Concanavalin A-like lectins/glucanases 49899 - Concanavalin A-like lectins/glucanases	0	DIRECT
81296,81296,81296 81296 - E set domains 81296 - E set domains 81296 - E set domains	0	DIRECT
49562,48371,56112 49562 - C2 domain (Calcium/lipid-binding domain, CaLB) 48371 - ARM repeat 56112 - Protein kinase-like (PK-like)	0	DIRECT
57196,49899,49899 57196 - EGF/Laminin 49899 - Concanavalin A-like lectins/glucanases 49899 - Concanavalin A-like lectins/glucanases	0	DIRECT
52058,52058,52058 52058 - L domain-like 52058 - L domain-like 52058 - L domain-like	0	DIRECT
54236,47031,50729 54236 - Ubiquitin-like 47031 - Second domain of FERM 50729 - PH domain-like	0	DIRECT
81660,56784,81665 81660 - Metal cation-transporting ATPase, ATP-binding domain N 56784 - HAD-like 81665 - Calcium ATPase, transmembrane domain M	0	DIRECT
69318,69179,69179 69318 - Integrin alpha N-terminal domain 69179 - Integrin domains 69179 - Integrin domains	0	DIRECT
57667,57667,57667 57667 - beta-beta-alpha zinc fingers 57667 - beta-beta-alpha zinc fingers 57667 - beta-beta-alpha zinc fingers	0.0001601	DIRECT
48726,48726,48726 48726 - Immunoglobulin 48726 - Immunoglobulin 48726 - Immunoglobulin	0.03929	INHERITED FROM: gustatory receptor neuron || commissure || prothoracic leg taste bristle || adult cerebral ganglion || synaptic neuropil || adult antennal lobe glomerulus || prothoracic leg taste bristle chemosensory neuron || tract neuropil || connective || s-LNv neuron || LNv neuron || leg taste bristle || adult brain
48726,48726,49265 48726 - Immunoglobulin 48726 - Immunoglobulin 49265 - Fibronectin type III	0.05581	INHERITED FROM: gustatory receptor neuron || lobe system of adult mushroom body || prothoracic leg taste bristle || antennal lobe glomerulus || adult antennal lobe glomerulus || neuropil associated CNS glial cell || prothoracic leg taste bristle chemosensory neuron || tract neuropil || giant fiber neuron || connective || s-LNv neuron || prothoracic leg sensillum || embryonic/larval central nervous system || LNv neuron || leg taste bristle || neuropil glial sheath
57196,57196,57196 57196 - EGF/Laminin 57196 - EGF/Laminin 57196 - EGF/Laminin	0.1188	INHERITED FROM: ocellar triangle || adult external head || tertiary pigment cell || gut section || adult peripheral nervous system || secondary pigment cell || photoreceptor cell R1 || eye photoreceptor cell stalk || postfrons || proventriculus || joint || photoreceptor cell R6 || ventral nervous system || ocellus || frons || articulation || wing blade dorsal compartment
46966,46966,46966 46966 - Spectrin repeat 46966 - Spectrin repeat 46966 - Spectrin repeat	0.1698	INHERITED FROM: ipsilateral tract || longitudinal connective || midgut enterocyte || tract || middle midgut || connective || copper cell
57196,57196,57184 57196 - EGF/Laminin 57196 - EGF/Laminin 57184 - Growth factor receptor domain	0.2295	INHERITED FROM: nerve || mesothoracic tergum || intersegmental nerve || adult external mesothorax || tergum || integumentary specialisation || scutum || dorsal mesothorax
49313,49313,49313 49313 - Cadherin-like 49313 - Cadherin-like 49313 - Cadherin-like	0.5873	INHERITED FROM: photoreceptor cell R4 || outer photoreceptor cell || wing hair

Trees by TreeVector

A presence/absence matrix is generated using protein domains and supradomains for all genomes in SUPERFAMILY. The RAxML software is used to produce a single, large tree topology using heuristic parsimony methods. Genome combinations, or specific clades, can be displayed as if individual trees had been produced. However, this data is extracted from the single large tree. This produces a higher quality topology than if the trees had been produced on their own, and allows the trees to be displayed instantly.